Biology Faculty Articles

Title

The Inoculum Effect and Band-Pass Bacterial Response to Periodic Antiobiotic Treatment

Document Type

Article

Publication Date

10-9-2012

Publication Title

Molecular Systems Biology

Keywords

Antibiotic, Bacteria, Bistability, Inoculum Effect

ISSN

1744-4292

Volume

8

Issue/No.

1

First Page

1

Last Page

11

Abstract

The inoculum effect (IE) refers to the decreasing efficacy of an antibiotic with increasing bacterial density. It represents a unique strategy of antibiotic tolerance and it can complicate design of effective antibiotic treatment of bacterial infections. To gain insight into this phenomenon, we have analyzed responses of a lab strain of Escherichia coli to antibiotics that target the ribosome. We show that the IE can be explained by bistable inhibition of bacterial growth. A critical requirement for this bistability is sufficiently fast degradation of ribosomes, which can result from antibiotic-induced heat-shock response. Furthermore, antibiotics that elicit the IE can lead to ‘band-pass’ response of bacterial growth to periodic antibiotic treatment: the treatment efficacy drastically diminishes at intermediate frequencies of treatment. Our proposed mechanism for the IE may be generally applicable to other bacterial species treated with antibiotics targeting the ribosomes.

Comments

Article #617

Additional Comments

Highlighted in "Editor's Choice": Microbiology - Hit'Em Quick, Hit'Em Strong (2012) Science, 338, 6104_x000D_ _x000D_ Highlighted in Durham Herald Sun_x000D_ _x000D_ Highlighted in Sharkbytes and Duke University Biomedical Engineering Research Article

This document is currently not available here.

Find in your library

Share

COinS